3,3'-iminodi(propylamine)

Endpoint summary

Description of key information

The oral LD50 was 700 mg/kg bw in rats.
The inhal. LC50 was ca. 0.03 mg/L air.
The dermal LD50 value falls between 200 and 400 mg/kg.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication which meets basic scientific principles.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

BASF-Test: The study was conducted according to an internal BASF method which in principle is comparable to the OECD Guideline 401.
A test group consisting of 5 animals/sex was treated by single gavage application with an aqueous solution of the test substance. The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 14 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Firma WIGA, Sulzfeld
- Weight at study initiation: male animals; 188g, female animals; 159 g
- Fasting period before study: 16 hours
- Diet: MRH-Kraftfutter from the Firma H . EGGERSMANN (Rinteln/Weser), ad libitum
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 4.64, 5.62, 6.81, 8.25, 10, 12.1 and 14.7 %

MAXIMUM DOSE VOLUME APPLIED: 1470 mg/kg

Doses:

464, 562, 681, 825, 1000, 1210 and 1470 mg/kg

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 1, 24, 48 hours, 7 and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 700 mg/kg bw

Based on:

test mat.

95% CL:

640 - 770

Sex:

male

Dose descriptor:

LD50

Effect level:

670 mg/kg bw

Based on:

test mat.

95% CL:

580 - 750

Sex:

female

Dose descriptor:

LD50

Effect level:

740 mg/kg bw

Based on:

test mat.

95% CL:

650 - 860

Mortality:

464 mg/kg: 0/10 males and 1/10 females after 14 days
562 mg/kg: 5/10 males and 3/10 females after 14 days
681 mg/kg: 4/10 males and 4/10 females after 14 days
825 mg/kg: 8/10 males and 4/10 females after 14 days
1000 mg/kg: 9/10 males and 8/10 females after 14 days
1210 and 1470 mg/kg: all animals died after 14 days

Clinical signs:

other: Dyspnoea, apathy, agitation, aggressive, lateral and dorsal position, staggering, atony, paresis, trembling, spastic movement, rolling cramps, fever convulsions, diarrhea, salivation, diminished general state.

Gross pathology:

Acute dilation of the heart, acute congestion hyperemia, diffuse reddening of glands mucosa of proventriculus, atonic intestine, diarrhea in intestine, sporadic diffuse reddening of the mucosa of the intestine, brightening of the kidneys.

Euthanasied animals
Slight brightening of the kidneys with gridlike pattern.

Executive summary:

In an oral toxicity study, comparable to OECD 401, dipropylenetriamine was administered to Sprague-Dawley rats (10animals/sex/dose) at 464 to 1470 mg/kg in single dosages (gavage) followed by a 14-day observation period.The LD50 was ca. 700 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

700 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study which meets basic scientific principles.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Firma WIGA (Sulzfeld)
- Weight at study initiation: 185 ± 15 gram
- Diet: Tieren Herilan MRH (Firma H . EGGERSMANN KG, Rinteln/Weser), ad libitum
- Water: ad libitum

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: ethanol

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: a constant quantity was ensured by a continuous infusion pump (UNITA I, B. BROWN, Melsungen) and by means of compressed air in a two-material nozzle which produces aerosols.
- Source and rate of air: 1000 L/h

TEST ATMOSPHERE
- Brief description of analytical method used: Gaschromatograph HP 5040 A with a 2 m glass colum (2 mm i.d.), with a Carbowax 20 M separation phase and Supelcoport 80/100 mesh carrier. The oventemperature is 200 °C, the detector (FID) and injector temperature are 280 °C, the corriergas flow is 20.4 ml/in, the hydrogen flow rate is 30 ml/min and the air flow is 255 ml/min. The retetion time of the internal standard (C17KW) is 2.66 min and the retetion time of the sample is 5.06.
- Samples taken from breathing zone: yes

CLASS METHOD
- Rationale for the selection of the starting concentration: First orientating dose was: 2.5 mg/L (analytical determined)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Nominal concentrations: 0.015, 0.037, 0.063, 0.47, 0.931, 4.66 and 8.37 mg/L
Measured concentrations: 0.014, 0.027, 0.055, 0.235, 0.606, 1.3 and 2.0 mg/L

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: before dosing, after 7 days and after 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.

Statistics:

Probability analyses from D.J. Finney ( D.J. Finney; Probitanalysis 1971, Seite 1-150). The LC50 was calculated with 95% probability.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

ca. 0.03 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Sex:

male

Dose descriptor:

LC50

Effect level:

0.04 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Sex:

female

Dose descriptor:

LC50

Effect level:

0.03 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

0.014 mg/L: none of the animals died after 14 days
0.027 mg/L: 3/10 males and 6/10 females after 14 days
0.055 mg/L: 8/10 males and 9/10 females after 14 days
0.235 mg/L and up: all animals died after 14 days

Clinical signs:

other: Red eye and nasal secretion, dyspnoea, imbalanced and insecure walk, crouched position, apathy, bad general condition, ragged and clotty fur, 2/10 females suffered hair loss, shaking, delayed pain reaction, cyanosis.

Body weight:

0.014 mg/L: normal body weight gain
0.027 mg/L: reduced body weight gain
0.055 mg/L: body weight loss

Gross pathology:

Diseased animals:
Acute dilatation of the heart, acute congested hyperemia, notable wet fleshy, edematous and diffuse redness of the lungs(bloody, lung hemorrhages), peripheral lobular pattern in the liver.

Euthanized animals:
0.014 mg/L: no abnormal findings
0.027 mg/L: carnification of the lungs
0.055 mg/L: strong weight loss, areas of carnification in the lungs

Executive summary:

In an inhalation toxicity study, comparable to OECD 403, Sprague-Dawley rats (10/sex/dose) were exposed (nose/head only) for 4 hours to 0.014 to 2.0 mg dipropylenetriamine aerosols/L air followed by an 14 day observation period. The LC50 was ca. 0.03 mg/L air.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

30 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication which meets basic scientific principles.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Firma WIGA (Sulzfeld)
- Weight at study initiation: male animals 140g, female animals 130g
- all animals are healthy with unharmed skin

Type of coverage:

occlusive

Vehicle:

olive oil

Details on dermal exposure:

TEST SITE
- Area of exposure: 5 cm2
- Type of wrap if used: aluminium foil fixed with stickytape

REMOVAL OF TEST SUBSTANCE
- Washing: with warm water or water/lutrol mixture
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 200, 400 and 640 mg/kg
- Concentration: 25% and 50%

Duration of exposure:

24 h

Doses:

200, 400 and 640 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 21 days
- Frequency of observations and weighing: 1 h, 1, 2, 8 , 14 and 21 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

200 - 400 mg/kg bw

Based on:

test mat.

Mortality:

200 mg/kg; none of the animals died after 14 days
400 mg/kg; 3/5 males and 5/5 females after 21 days
640 mg/kg: all animals died after 24 h

Clinical signs:

other: Apathy, 24 hours after application necrosis was observed on all animals

Gross pathology:

Diseased animals
400-640 mg/kg: dilation and acute congestion hyperaemia of the heart, obvious almost infarctious bloody lungs
640 mg/kg: bright kidneys

Euthanized animals
No abnormal findings

Executive summary:

In a dermal toxicity study, comparable to OECD 402, dipropylenetriamine was applied in olive oil occlusively at single doses of 200 to 640 mg/kg to Sprague-Dawley rats (5/sex/dose).

The LD50 falls between 200 and 400 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

200 mg/kg bw

Additional information

Oral toxicity

In an oral toxicity study, comparable to OECD 401, Sprague-Dawley rats (10/sex/dose) were administered dipropylenetriamine at 464 to 1470 mg/kg by single dose (gavage) followed by a 14-day observation period (BASF AG, 1977). Clinical signs included dyspnoea, apathy, agitation, aggressive, lateral and dorsal position, staggering, atony, paresis, trembling and spastic movement, rolling cramps, fever convulsions, diarrhea, salivation and a diminished general state. Findings at necropsy included acute dilation of the heart, acute congestion hyperemia, diffuse reddening of glands mucosa of proventriculus, atonic intestine, diarrhea in intestine, sporadic diffuse reddening of the mucosa of the intestine and brightening of the kidneys. The LD50 was ca. 700 mg/kg bw.

 

Inhalation toxicity

In an inhalation toxicity study, comparable to OECD 403, Sprague-Dawley rats (10/sex/dose) were exposed (nose/head only) for 4 hours to 0.014 to 2.0 mg dipropylenetriamine aerosols/L air followed by an 14 day observation period (BASF AG, 1979). Clinical signs included red eye and nasal secretion, dyspnoea, imbalanced and insecure walk, crouched position, apathy, bad general condition, ragged and clotty fur, 2/10 females suffered hair loss, shaking, delayed pain reaction, cyanosis. Findings at necropsy included acute dilatation of the heart, acute congested hyperemia, notable wet fleshy, edematous and diffuse redness of the lungs and peripheral lobular pattern in the liver in animals that died during the study. The LC50 was ca. 0.03 mg/L air.

In another study in which rats were exposed for 7 hours to a saturated dipropylenetriamine atmosphere (concentration not given) at 20 °C no deaths were observed during a 14-day observation period (BASF AG, 1978a).

 

Dermal toxicity:

In a dermal toxicity study, comparable to OECD 402, dipropylenetriamine was applied in olive oil occlusively at single doses of 200 to 640 mg/kg to Sprague-Dawley rats (5/sex/dose).

(BASF AG, 1978b). Clinical signs included apathy and 24 hours after application necrosis was observed at all animals. Findings at necropsy included dilation and acute congestion hyperaemia of the heart, obvious almost infarctious bloody lungs and brightening of the kidneys in animals that died during the study. No abnormal pathology was observed in euthanized animals. The LD50 falls between 200 and 400 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Reliable guideline compliant study.

Justification for selection of acute toxicity – inhalation endpoint
Reliable guideline compliant study.

Justification for selection of acute toxicity – dermal endpoint
Reliable guideline compliant study.

Justification for classification or non-classification

N-(3-aminopropyl)propane-1,3-diamine is included in Annex VI of Regulation 1272/2008/EC with the following classification:

Table 3.1: acute oral tox. 4*, H 302; acute dermal tox. 3*, H311; acute inhalation tox. 2*, H330

Table 3.2: R22/24/26

Based on the available data the test item is subject to C&L

according to Regulation 1272/2008/EC: acute oral tox. 4, H302; acute dermal tox. 3, H311; acute inhalation tox. 1, H330

according to Directive 67/548/EEC: acute oral tox.: R22; acute dermal tox.: R24, acute inhalation tox: R26